Sling vs Botox for Mixed Incontinence

Phase 3

Completed

Conditions: Urinary Incontinence, Stress
Urinary Incontinence, Urge

Interventions: Device: Mid-urethral sling
Drug: Botox® injection

Registration Number: NCT04171531

Lead Sponsor: NICHD Pelvic Floor Disorders Network

Brief Summary: The primary aim is to compare the effectiveness of intradetrusor injection of 100 unit injection of Botulinum toxin A to mid-urethral sling for change in MUI symptoms 6 months following treatment.

Detailed Description: Mixed urinary incontinence (MUI), defined as the presence of both stress urinary incontinence (SUI) and urgency urinary incontinence (UUI), is a challenging condition for which clinicians frequently use multiple sequential treatments that have undergone limited evaluation in rigorous clinical trials. The Mixed Urinary Incontinence: Mid-urethral Sling vs. Botox A (MUSA) trial will estimate the effect of Botulinum toxin A (Botox A ®) compared to mid-urethral sling for the treatment of MUI symptoms in 146 women. MUSA is a randomized 2-arm clinical trial.

The purpose of MUSA is to:

* compare treatment with either Botulinum toxin A (Botox A ®) or mid-urethral sling for women with MUI

* characterize patient characteristics associated with treatment response

The primary objective is to estimate the effect of intradetrusor injections Botulinum toxin A (Botox A ®) compared to mid-urethral sling for treatment of MUI in 146 women 6 months after treatment. The change in severity of MUI symptoms will be measured using the Urogenital Distress Inventory.

Secondary outcomes include:

• Urogenital Distress Inventory Stress and Irritative subscales

Other outcomes include:

* Urogenital Distress Inventory Obstructive subscale

* Patient bladder diary metrics including numbers of daily incontinence episodes and voids and voiding frequency

* Other patient reported outcomes/validated instruments and associated scales and subscales: EQ-5D, IIQ-LF, OABq-LF, OAB-SATq, PISQ-IR, PGI-I, PGI-S, PGSC, and SF-36

* Physical measures of effectiveness: Postvoid Residual Volume

The study will continue with an additional 6 month observational period until 12 months post treatment.

A supplemental study will characterize baseline putative proteins/protein pathways in women with MUI associated with change in UDI after treatment with MUS or onabotulinum toxin A. Those results are not reported with this record.

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 150

Inclusion Criteria

Reporting at least "moderate bother" from UUI item on UDI

* "Do you experience urine leakage associated with a feeling of urgency?"
Reporting at least "moderate bother" from SUI item on UDI

* "Do you experience urine leakage related to physical activity, coughing, or sneezing?"
Diagnosis of SUI defined by a positive cough stress test (CST) or UDE within the past 18 months
Presence of UUI on bladder diary with > 4 Urgency IE/3-day diary
Urinary symptoms >3 months
Persistent symptoms despite at least one or more conservative treatments (e.g. supervised behavioral therapy, physical therapy) as determined adequate by the physician.
Inadequate response to oral overactive bladder medications (including anti-cholinergic and/or beta-mimetic medication) unless patient is
1. intolerant of oral overactive bladder medications, or
2. oral overactive bladder medications are contraindicated as determined by the treating provider.
Urodynamics within past 18 months
Demonstrates ability (or have caregiver demonstrate ability) to perform clean intermittent self-catheterization.

Exclusion Criteria

Anterior or apical compartment prolapse at or beyond the hymen (>0 on POPQ), regardless if patient is symptomatic

* Women with anterior or apical prolapse above the hymen (<0) who do not report vaginal bulge symptoms will be eligible
Planned concomitant surgery for anterior vaginal wall or apical prolapse > 0

* Women undergoing only rectocele repair or other repair unrelated to anterior or apical compartment are eligible
Women undergoing hysterectomy for any indication will be excluded
Active pelvic organ malignancy
Age <21 years
Pregnant or plans for future pregnancy in next 6 months, or within 12 months post-partum
Post-void residual >150 cc on 2 occasions within the past 6 months, or current catheter use
Participation in other trial that may influence results of this study
Unevaluated hematuria
Prior sling, synthetic mesh for prolapse, implanted nerve stimulator for urinary incontinence
Spinal cord injury or advanced/severe neurologic conditions including Multiple Sclerosis, Parkinsons, Myasthenia Gravis, Charcot-Marie-Tooth
Women on overactive bladder medication/therapy will be eligible after 3 week wash-out period
Non-ambulatory
History of serious adverse reaction to synthetic mesh
Not able to complete study assessments per clinician judgment, or not available for 6 month follow-up
Diagnosis of and/or history of bladder pain or chronic pelvic pain
Women who had intravesical Botox injection within the past 12 months
Women who have undergone anterior or apical pelvic organ prolapse repair within the past 6 months

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Mid-urethral sling	Mid-urethral sling	Mid-urethral Sling Procedure includes retropubic as well as transobturator full length slings. Follow up visits at 2 weeks, 3 and 6 months post intervention to collect clinical and patient-reported outcomes.
Botox A® injection	Botox® injection	A dose of 100 units of Botulinum toxin A will be injected into the bladder. Follow up visits at 2 weeks, 3 and 6 months post intervention to collect clinical and patient-reported outcomes.

Primary Outcome Measures

Name	Time	Method
UDI-LF Total Score Change From Baseline	3, 6, 9, and 12 Months	The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI scale has a range from 0 to 300 with higher scores indicating greater distress. The outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline.

Secondary Outcome Measures

Name	Time	Method
UDI-LF Irritative Score Change From Baseline	3, 6, 9, and 12 Months	The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI Irritative subscale has a range from 0 to 100 with higher scores indicating greater distress. The outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline.
UDI-LF Stress Score Change From Baseline	3, 6, 9, and 12 Months	The Urogenital Distress Inventory is a standardized a measure of overactive bladder symptoms and health-related quality of life. The UDI Stress subscale has a range from 0 to 100 with higher scores indicating greater distress. The outcome is calculated as the difference in score at 3, 6, or 12 months and the score at baseline.

Trial Locations

Locations (8): University of Alabama at Birmingham, Department of Obstetrics and Gynecology
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Birmingham, Alabama, United States
University of California at San Diego
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La Jolla, California, United States
Duke University, Duke Division of Urogynecology and Reconstructive Pelvic Surgery
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Durham, North Carolina, United States
University of Pennsylvania
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Philadelphia, Pennsylvania, United States
Magee-Women's Hospital, Department of Obstetrics and Gynecology
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Pittsburgh, Pennsylvania, United States
Kaiser Permanente
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San Diego, California, United States
University of Texas Southwestern Medical Center
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Dallas, Texas, United States
Brown/ Women and Infants Hospital of Rhode Island, Center for Women's Pelvic Medicine and Reconstructive Surgery
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Providence, Rhode Island, United States